The unusually low pKa of the methylene protons of Meldrum's acid (2,2-dimethyl-1,3-dioxane-4,6-dione; A. N. Meldrum, J. Chem. Soc., 93, 598 (1908)) and the ability of its ester groups to undergo hydrolysis under very mild conditions make it an excellent alternative for malonic acid in reactions in which vigorous conditions are to be avoided. Reactions of this species with carbonyl compounds and some alkyl halides have been reported (D. Davidson and S. A. Bernhard, J. Am. Chem. Soc., 70, 3426 (1948); E. J. Corey, J. Am. Chem. Soc., 74, 5897 (1952); H. R. Snyder and C. W. Kruse, J. Am. Chem. Soc., 80, 1942 (1958); J. W. Hedge, C. W. Kruse, and H. R. Snyder, J. Org. Chem., 26, 3166 (1961)).
Methylene Meldrum's acid (II) has been reported as a compound with high reactivity as a dienophile, as well as a Michael acceptor. (H. McNab, Chem. Soc. Rev., 7, 345 (1978); F. J. Kunz and O. E. Polansky, Monatsh. Chem., 100, 920 (1969); R. F. C. Brown, F. W. Eastwood, and G. L. McMullen, Aust. J. Chem., 30, 179 (1977)). This species, however, can only be generated in situ as an intermediate and cannot be isolated. In Diels-Alder reactions, for instance, it is generated in a one-pot reaction by adding a 37% aqueous solution of formaldehyde to a solution containing the diene and Meldrum's acid. Diisopropylidene methylenedimalonate (III), the aldol-Michael bis adduct of Meldrum's acid and formaldehyde, has been shown to be a source of methylene Meldrum's acid for the addition of substituted three-carbon units to monohydroxyanthraquinones in Michael-type reactions (Mitscher, et al., Tetrahedron Letters, 26, 3195 (1985)). ##STR1## It has also been shown that III and one equivalent of formaldehyde improve the yields of Diels-Alder reactions when used instead of Meldrum's acid and formaldehyde. The mechanism by which this reaction proceeds presumably involves the addition of formaldehyde to one of the two Meldrum's acids at the 5-position, followed by cleavage of the C--C bond and elimination of water to give two methylene Meldrum's units as shown in the following "speculative" mechanism suggested by J. F. Buzinkai, et al., Tetrahedron Letters, 26, 3195 (1985): ##STR2## For all intents and purposes, III is a protected form of methylene Meldrum's acid which enhances the yields of Diels-Alder reactions, but not without side products. III has not proved to be very effective in Michael reactions.
This invention provides compounds which are new stabilized precursors of methylene Meldrum's acid which greatly enhance the yields of reactions which would normally involve methylene Meldrum's acid.